| Abstract: |
Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In Staphylococcus aureus, SprC is an antivirulent trans-acting sRNA known to base-pair with the major autolysin atlmRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing, we looked for its sRNA-RNA interactome and identified 14 novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrBand deoD,and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC-czrBinteraction pinpointed a destabilization of the czrABcotranscript, leading to a decrease of the mRNA level that impaired CzrB zinc efflux pump expression. On a physiological standpoint, we showed that SprC expression is detrimental to combat against zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrBmRNA levels in a sprC-deleted mutant, indicating a functional link between SprC and czrBupon internalization in macrophages, and suggesting a role in resistance to both oxidative and zinc bursts. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies used by S. aureusto balance virulence using an RNA regulator. |
